Cancer is a disease that claims a large number of lives each year. For many types of cancer the best currently-known treatments are only partially effective. For example, each year 500,000 people worldwide are diagnosed with head and neck squamous cell carcinoma (HNSC). The 5-year survival rate has remained unchanged at about 50% for the past few decades. For many types of cancer, early detection and treatment are critical to improving the survival rate.
Medical systems around the world lack the financial and other resources to closely follow all patients who have lesions that could be pre-cancerous. A tool capable of evaluating the risk that a lesion will develop into cancer would allow medical resources to be directed in a more focussed manner. For example, the majority (˜90%) of oral pre-malignant lesions (OPLs) do not progress to invasive oral squamous cell carcinoma. A method for determining which OPLs will progress to cancer would allow at-risk patients to be followed closely to permit earlier intervention (e.g. surgery, chemoprevention or radiation etc.) with improved survival outcomes. OPLs are pre-neoplastic lesions of the oral cavity. OPLs include conditions described in the field as oral epithelial dysplasia; mild dysplasia; leukoplakia; erythroplakia; hyperplasia, moderate dysplasia; low-grade dysplasia; and, high grade dysplasia.
Current methods for detecting many types of cancer require skilled human intervention. For example, many types of cancer screening are performed by a pathologist or cytotechnologist who examines images of tissue samples for cells that look abnormal to the trained eye.
Standard histopathological grading involves classifying tissues into various categories. for example, OPLs may be classified into the categories “Normal”; “Hyperplasia”; Mild Dysplasia”; “Moderate Dysplasia”; “Severe Dysplasia” and “Squamous Cell Carcinoma”. Standard histopathological grading does not correlate well with progression or patient outcome for low-grade lesions and therefore has low prognostic value. Because histological grading involves the application of human judgment, the results are not consistently reproducible. Further, these tissue assessment methods have the disadvantage that they are time consuming and expensive to implement and tend to be qualitative rather than quantitative.
Other techniques for the assessment of tissues (such as loss of heterozygosity (“LOH”) measurements, molecular biomarkers, imaging, may provide some prognostic information but are either too slow, costly (or both) to be readily implemented clinically. Further, some such methods can only be performed for lesions that are large enough to provide enough tissue for molecular analysis.
It has been found that LOH patterns can be used to classify OPLs that are not distinguishable by histopathological grading according to cancer risk. Rosin, M. P., et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res, 6: 357-362, 2000 used LOH to classify OPLs having minimal (mild/moderate) or no dysplasias into different risk categories. Compared with OPLs without LOH at 3p and 9p (low-risk), those with LOH at 3p and/or 9p but not in other arms (intermediate-risk) demonstrated a 3.8-fold increase in relative cancer risk. OPLs with LOH at 3p and/or 9p plus additional losses (at 4q, 8p, 11q, or 17p, high-risk) demonstrated 33-fold increases in relative cancer risk.
Despite the billions of dollars that have been spent worldwide on cancer research, there is currently, and has been for many years, an urgent need for practical ways to do one or more of:                detect cancer;        assess the malignant potential of lesions;        assess the likely response of a particular cancer to treatment; and,        assess the disease prognosis (e.g. survival or likelihood of progression to cancer within a time period) of affected patients.There is a particular need for such ways in relation to oral cancers.        